A Phase 1b/2a clinical trial of NDV-3A
vaccine containing a Candida albicans recombinant Als3
protein formulated with
alum protected women <40 years old from recurrent
vulvovaginal candidiasis (RVVC). We investigated the potential use of anti-Als3p sera as
surrogate marker of NDV-3A efficacy. Pre- and post-vaccination sera from subjects who experienced recurrence of
vulvovaginal candidiasis (R) vs. those who were recurrence-free [non-recurrent (NR)] were evaluated. Anti-Als3p
antisera obtained were evaluated for (1) titer and subclass profile and (2) their ability to influence C. albicans virulence traits including hyphal elongation, adherence to
plastic, invasion of vaginal epithelial cells, biofilm formation on
plastic and
catheter material, and susceptibility to neutrophil killing in vitro. Serum
IgG titers in NR patients were consistently higher than in R patients, particularly for anti-Als3 subclass
IgG2. Sera from vaccinated NR patients reduced hyphal elongation, adhesion to
plastic, invasion of vaginal epithelial cells, and biofilm formation significantly more than pre-
immune sera, or sera from R- or placebo-group subjects. Pre-adsorption of sera with C. albicans germ tubes eliminated these effects, while heat inactivation did not. Finally, sera from NR subjects enhanced neutrophil-mediated killing of C. albicans relative to pre-
immune sera or sera from R patients. Our results suggest that higher Als3p antibody titers are associated with protection from RVVC, attenuate C. albicans virulence, and augment immune clearance of the fungus in vitro. Thus, Als3p serum
IgG antibodies are likely useful markers of efficacy in RVVC patients vaccinated with NDV-3A.